| Eligibility |
Inclusion Criteria:
- Subject have provided informed consent
- Male or female = 21 to = 65years of age at signing of informed consent
- Moderate-severe anxiety or depression related to cancer as measured by the
GRID-HAM-D17 (depression) or the HAM-A (anxiety)
- Prescribed a radiation therapy course with palliative intent. Radiation therapy will
be given priority with respect to scheduling and delivery over appointments related to
KAP. Patients may begin the KAP process as soon as they are able after enrollment as
long as it does not interfere with or delay receipt of radiation therapy. The timing
of KAP/ RT can be either concurrent or sequential with RT coming first based on
convenience to the patient and treatment teams, although completing the treatment
expediently will be encouraged. Total treatment package time should be less than 3
months from CT simulation.
- A female subject of childbearing potential who is sexually active with a
non-sterilized male partner must agree to consistently and correctly use a highly
effective method of contraception with a failure rate of < 1% per year (Appendix 1)
during the study and for at least 90 days after study drug administration. If a
hormonal contraceptive is used, it must have been initiated at least 1 month before
dosing.
- Negative pregnancy test (women only)
- Female subject of non-childbearing potential must be either: surgically sterile
(hysterectomy, tubal ligation, or bilateral oophorectomy), or post-menopausal with
amenorrhea for at least 2 years and documented follicle-stimulating hormone (FSH)
levels =30 mIU/mL, or mL or must use a medically accepted double-barrier contraceptive
method during the study and for at least 90 days after study drug administration.
- Male subject must agree to use prophylactic contraception
- Patients receiving chemotherapy, hormonal therapy, radiation therapy, biologic
therapies may participate while receiving those therapies. Continuing hormonal
therapy, chemotherapy, or radiation treatment is acceptable if the patient is
tolerating the therapy or treatment in a sufficient fashion to allow administration of
intramuscular ketamine
- Agree that for one week preceding each KAP session, he/she will refrain from taking
any nonprescription medication, nutritional supplement, or herbal supplement except
when approved by the research team. Exceptions will be evaluated by the research team
and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common
doses of vitamins and minerals
- Agree not to use nicotine for at least 2 hours before KAP administration, and not
again until questionnaires have been completed approximately 7 hours after KAP
administration.
- Agree to consume approximately the same amount of caffeine-containing beverage (e.g.,
coffee, tea) that he/she consumes on a usual morning, before arriving at the research
unit on the mornings of KAP session days. If the patient does not routinely consume
caffeinated beverages, he or she must agree not to do so on KAP session days.
- Agree not to take any PRN medications on the mornings of KAP sessions, with the
exception of daily opioid pain medication. Non-routine PRN medications for treating
breakthrough pain that were taken in the 24 hours before the KAP session may result in
rescheduling the treatment session, with the decision at the discretion of the
investigators.
- Agree to refrain from using any psychoactive drugs, including alcoholic beverages,
within 24 hours of each KAP administration. As described elsewhere, exceptions include
daily use of caffeine, nicotine, and opioid pain medication.
- Willingness to not driving for 24 hours following study drug administration
- English proficiency
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Karnofsky Performance Scale (KPS) index of 60 or less
- Patients will be excluded if they are in treatment in another clinical trial involving
an investigational product for treatment of cancer.
- Hepatic dysfunction as indicated by the following values:
- -- GGT > 3 x ULN (upper limit of norm)
- -- AST > 3 x ULN
- -- ALT > 3 x ULN
- -- Tot Bili > 3.0 mg/dl
- Known paraneoplastic syndrome or "ectopic" hormone production by the primary tumor
such as the patient could have or be at risk for hypercalcemia, Cushing's syndrome,
hypoglycemia, syndrome of inappropriate antidiuretic hormone secretion, or carcinoid
syndrome
- Cardiovascular conditions: uncontrolled hypertension, angina, a clinically significant
ECG abnormality (e.g. atrial fibrilation), TIA in the last 6 months, stroke,
peripheral or pulmonary vascular disease (no active claudication)
- Systolic blood pressure >140mmHG or < 85 mmHg or diastolic blood pressure >90mmHg or
heart rate of > 110 beat per minutes. Pulse oximetry of 94% or less.
- Epilepsy with history of seizures
- Renal insufficiency (creatinine clearance < 40 ml/min using the Cockraft and Gault
equation)
- Uncontrolled hyperthyroidism (low thyroid stimulating hormone with high T3 or T4)
- Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of
hypoglycemia
- Opioid pain medications (e.g. oxycodone sustained release, morphine sustained release
-- which are usually taken at 12 hour intervals) will be allowed if the last dose
occurred at least 12 hours before KAP administration; such medication will not be
taken again until at least 6 hours after KAP administration.
- Current or history of schizophrenia, psychotic disorder, bipolar disorder, delusional
disorder, paranoid personality disorder, substance use disorder, schizoaffective
disorder, or borderline personality disorder, as assessed by medical history. Patients
who have bipolar disorder but are not currently in a manic state may be included based
on judgement of investigators.
- Patients with first or second-degree relatives with schizophrenia, non-substance
induced psychotic disorder, or bipolar disorder
- Increased risk of intracranial pressure:
- Recent ischemic or hemorrhagic cerebral vascular accident in the last 1 month.
- Brain tumors with symptoms and signs of increased intracranial pressure.
- Seizure in the last 6 months.
- Head trauma with symptoms of increased intracranial pressure.
- Hydrocephalus.
- Uncontrolled nausea/vomiting/headache or = grade 3 nausea despite one line of
antiemetics
- Recent traumatic brain injury
- Potential for adverse drug-drug interactions. Concomitant medications with significant
potential to interact with study medications will be exclusionary if they cannot be
tapered. These include the following:
- Regular benzodiazepine usage greater than 0.5mg of clonazepam/day or equivalent which
cannot be stopped 1 day prior to ketamine injection
- Lamotrigine usage
- Usage of methylphenidate, phenobarbital, or amphetamine drugs within 5 half-lives of
KAP
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to ketamine or ketamine sensitivity
- Severe depression/anxiety which warrants immediate treatment with antidepressant or
anxiolytic medication due to suicidal ideation
- History of alcoholism or drinking more than an average of 2 alcoholic beverage per day
within past 5 years
- Female subject of childbearing potential who is not willing to use effective methods
of birth controls or practice sexual abstinence up to 10 days following the last
administration of ketamine.
- A positive pregnancy test at Screening
- History or evidence of any other clinically significant disorder, condition, or
disease that in the opinion of the investigator or based on psychotherapist opinion
would pose a risk to the subject safety or interfere with the study evaluation,
procedure, or completion.
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